Diabetes during pregnancy results in congenital malformations and long-term postnatal diseases. Experimental models are still needed to investigate the mechanism responsible for these alterations. Thus, by the administration of different doses of
streptozotocin (STZ) (0, 25, 30, or 35 mg/kg
body weight, intravenous) at the onset of pregnancy in rats, the present study sought an appropriate animal model for this pathology. At day 6 of pregnancy, plasma
glucose was progressively higher with an increasing STZ dose, and in rats receiving the 35-mg dose, 2 subgroups were detected: some animals had plasma
glucose levels above controls but below 200 mg/dL (mildly diabetic, MD), whereas others had levels above 400 mg/dL (severely diabetic, SD). At day 20 of pregnancy, the MD rats had normal glycemia, but after an oral
glucose load (2 g/kg
body weight), plasma
glucose increased more and
insulin increased less than in controls. The SD rats maintained their
hyperglycemia and had a greatly impaired oral
glucose tolerance. At day 20, fetuses of SD dams were fewer, weighed less, and had enhanced plasma
glucose and
triglycerides and decreased
insulin, whereas those from MD dams did not differ from controls. At birth, newborns from MD dams had higher
body weight, plasma
insulin, and liver
triglycerides as well as total body
lipid concentrations than controls, and on day 21, remained macrosomic and showed higher plasma
glucose and liver
triglyceride concentrations. At 70 days of age, offspring of MD dams had impaired oral
glucose tolerance but normal plasma
insulin change in the case of females, whereas plasma
insulin increased less in males. These alterations were manifest more in those offspring from dams that had >50% macrosomic newborns than in those from dams that had <50% macrosomic newborns. In conclusion, whereas our MD rats mimic the changes taking place in gestational diabetic women and show the long-term risk of macrosomia, the SD rats are more similar to uncontrolled diabetics. Thus these two rat models, obtained with moderate amounts of STZ, could be used to study the pathophysiological consequences of these different diabetic conditions.